Shared and distinct genetics of pure type 1 diabetes and type 1 diabetes with celiac disease, homology in their auto-antigens and immune dysregulation states: a study from North India.
Celiac disease
Epitopes
Genetic polymorphism
Immune dysfunction
Type 1 diabetes
Journal
Acta diabetologica
ISSN: 1432-5233
Titre abrégé: Acta Diabetol
Pays: Germany
ID NLM: 9200299
Informations de publication
Date de publication:
14 Mar 2024
14 Mar 2024
Historique:
received:
26
09
2023
accepted:
11
02
2024
medline:
14
3
2024
pubmed:
14
3
2024
entrez:
14
3
2024
Statut:
aheadofprint
Résumé
This study was undertaken to explicate the shared and distinctive genetic susceptibility and immune dysfunction in patients with T1D alone and T1D with CD (T1D + CD). A total of 100 T1D, 50 T1D + CD and 150 healthy controls were recruited. HLA-DRB1/DQB1 alleles were determined by PCR-sequence-specific primer method, SNP genotyping for CTLA-4 and PTPN22 was done by simple probe-based SNP-array and genotyping for INS-23 Hph1 A/T was done by RFLP. Autoantibodies and cytokine estimation was done by ELISA. Immune-regulation was analysed by flow-cytometry. Clustering of autoantigen epitopes was done by epitope cluster analytical tool. Both T1D alone and T1D + CD had a shared association of DRB1*03:01, DRB1*04, DRB3*01:07/15 and DQB1*02. DRB3*01:07/15 confers the highest risk for T1D with relative risk of 11.32 (5.74-22.31). Non-HLA gene polymorphisms PTPN22 and INS could discriminate between T1D and T1D + CD. T1D + CD have significantly higher titers of autoantibodies, expression of costimulatory molecules on CD4 and CD8 cells, and cytokine IL-17A and TGF-β1 levels compared to T1D patients. Epitopes from immunodominant regions of autoantigens of T1D and CD clustered together with 40% homology. Same HLA genes provide susceptibility for both T1D and CD. Non-HLA genes CTLA4, PTPN22 and INS provide further susceptibility while different polymorphisms in PTPN22 and INS can discriminate between T1D and T1D + CD. Epitope homology between autoantigens of two diseases further encourages the two diseases to occur together. The T1D + CD being more common in females along with co-existence of thyroid autoimmunity, and have more immune dysregulated state than T1D alone.
Identifiants
pubmed: 38483572
doi: 10.1007/s00592-024-02258-5
pii: 10.1007/s00592-024-02258-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.
Références
Das AK (2015) Type 1 diabetes in India: overall insights. Indian J Endocrinol Metab 19(Suppl 1):S31. https://doi.org/10.4103/2230-8210.155372
doi: 10.4103/2230-8210.155372
pubmed: 25941645
pmcid: 4413384
Bhadada SK, Kochhar R, Bhansali A et al (2011) Prevalence and clinical profile of celiac disease in type 1 diabetes mellitus in north India. J Gastroenterol Hepatol 26(2):378–381. https://doi.org/10.1111/j.1440-1746.2010.06508.x
doi: 10.1111/j.1440-1746.2010.06508.x
pubmed: 21261730
Singh P, Seth A, Kumar P, Sajjan S (2017) Coexistence of celiac disease & type 1 diabetes mellitus in children. Indian J Med Res 145(1):28. https://doi.org/10.4103/ijmr.IJMR_199_15
doi: 10.4103/ijmr.IJMR_199_15
pubmed: 28574011
pmcid: 5460569
Albatineh A, Dehvan F, Shariari H, Moradi Y, Moradveisi B, Gheshlagh RG (2021) Prevalence of celiac disease in patients with type 1 diabetes: a systematic review and meta-analysis. Clin Diabetol 10(6):447–461. https://doi.org/10.5603/DK.2021.0055
doi: 10.5603/DK.2021.0055
Gomes KFB, Santos AS, Semzezem C et al (2017) The influence of population stratification on genetic markers associated with type 1 diabetes. Sci Rep 7(1):43513. https://doi.org/10.1038/srep43513
doi: 10.1038/srep43513
pubmed: 28262800
pmcid: 5338024
Robertson CC, Inshaw JRJ, Onengut-Gumuscu S et al (2021) Fine-mapping, trans-ancestral and genomic analyses identify causal variants, cells, genes and drug targets for type 1 diabetes. Nat Genet 53(7):962–971. https://doi.org/10.1038/s41588-021-00880-5
doi: 10.1038/s41588-021-00880-5
pubmed: 34127860
pmcid: 8273124
Li M, Wang S, Xu K et al (2020) High prevalence of a monogenic cause in Han Chinese diagnosed with type 1 diabetes, partly driven by nonsyndromic recessive WFS1 mutations. Diabetes 69(1):121–126. https://doi.org/10.2337/db19-0510
doi: 10.2337/db19-0510
pubmed: 31658956
Monar GVF, Islam H, Puttagunta SM et al (2022) Association between type 1 diabetes mellitus and celiac disease: autoimmune disorders with a shared genetic background. Cureus. https://doi.org/10.7759/cureus.22912
doi: 10.7759/cureus.22912
Sahin Y (2021) Celiac disease in children: a review of the literature. World J Clin Pediatr 10(4):53. https://doi.org/10.5409/wjcp.v10.i4.53
doi: 10.5409/wjcp.v10.i4.53
pubmed: 34316439
pmcid: 8290992
Frisk G, Hansson T, Dahlbom I, Tuvemo T (2008) A unifying hypothesis on the development of type 1 diabetes and celiac disease: gluten consumption may be a shared causative factor. Med Hypotheses 70(6):1207–1209. https://doi.org/10.1016/j.mehy.2007.05.058
doi: 10.1016/j.mehy.2007.05.058
pubmed: 18249499
Smyth DJ, Plagnol V, Walker NM et al (2008) Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med 359(26):2767–2777. https://doi.org/10.1056/NEJMoa0807917
doi: 10.1056/NEJMoa0807917
pubmed: 19073967
pmcid: 2840835
O’Neill RE, Cao X (2019) Co-stimulatory and co-inhibitory pathways in cancer immunotherapy. Adv Cancer Res 143:145–194. https://doi.org/10.1016/bs.acr.2019.03.003
doi: 10.1016/bs.acr.2019.03.003
pubmed: 31202358
pmcid: 7336166
Arif S, Moore F, Marks K et al (2011) Peripheral and islet interleukin-17 pathway activation characterizes human autoimmune diabetes and promotes cytokine-mediated β-cell death. Diabetes 60(8):2112–2119. https://doi.org/10.2337/db10-1643
doi: 10.2337/db10-1643
pubmed: 21659501
pmcid: 3142078
Honkanen J, Nieminen JK, Gao R et al (2010) IL-17 immunity in human type 1 diabetes. J Immunol 185(3):1959–1967. https://doi.org/10.4049/jimmunol.1000788
doi: 10.4049/jimmunol.1000788
pubmed: 20592279
Qiu AW, Cao X, Zhang WW, Liu QH (2021) IL-17A is involved in diabetic inflammatory pathogenesis by its receptor IL-17RA. Exp Biol Med 246(1):57–65. https://doi.org/10.1177/1535370220956943
doi: 10.1177/1535370220956943
Abdel-Moneim A, Bakery HH, Allam G (2018) The potential pathogenic role of IL-17/Th17 cells in both type 1 and type 2 diabetes mellitus. Biomed Pharmacother 101:287–292. https://doi.org/10.1016/j.biopha.2018.02.103
doi: 10.1016/j.biopha.2018.02.103
pubmed: 29499402
Cicerone C, Nenna R, Pontone S (2015) Th17, intestinal microbiota and the abnormal immune response in the pathogenesis of celiac disease. Gastroenterol Hepatol Bed Bench 8(2):117. https://doi.org/10.22037/ghfbb.v8i2.728
doi: 10.22037/ghfbb.v8i2.728
pubmed: 25926936
pmcid: 4404588
Kaur N, Minz RW, Bhadada SK, Dayal D, Singh J, Anand S (2017) Deranged regulatory T-cells and transforming growth factor-β1 levels in type 1 diabetes patients with associated autoimmune diseases. J Postgrad Med 63(3):176. https://doi.org/10.4103/jpgm.JPGM_608_16
doi: 10.4103/jpgm.JPGM_608_16
pubmed: 28695870
pmcid: 5525482
Husby S, Koletzko S, Korponay-Szabó IR et al (2012) European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 54(1):136–160. https://doi.org/10.1097/MPG.0b013e31821a23d0
doi: 10.1097/MPG.0b013e31821a23d0
pubmed: 22197856
Joshi R, Madvariya M (2015) Prevalence and clinical profile of celiac disease in children with type 1 diabetes mellitus. Indian J Endocrinol Metab 19(6):797. https://doi.org/10.4103/2230-8210.167555
doi: 10.4103/2230-8210.167555
pubmed: 26693431
pmcid: 4673809
Lionel B, Mathai S, Simon A, Joseph A (2020) Clinical manifestations of celiac disease in children with type 1 diabetes mellitus-an institutional experience from Southern India. J Clin Diagnostic Res. https://doi.org/10.7860/JCDR/2020/43056.13500
doi: 10.7860/JCDR/2020/43056.13500
Ganji A, Moghbeli M (2018) Type 1 diabetes and hyperthyroidism in a family with celiac disease after exposure to gluten: a rare case report. Clin Diabetes Endocrinol 4:1–3. https://doi.org/10.1186/s40842-018-0075-2
doi: 10.1186/s40842-018-0075-2
Barker JM, Liu E (2008) Celiac disease: pathophysiology, clinical manifestations, and associated autoimmune conditions. Adv Pediatr 55:349–365. https://doi.org/10.1016/j.yapd.2008.07.001
doi: 10.1016/j.yapd.2008.07.001
pubmed: 19048738
pmcid: 2775561
Rani R, Sood A, Goswami R (2004) Molecular basis of predisposition to develop type 1 diabetes mellitus in North Indians. Tissue Antigens 64(2):145–155. https://doi.org/10.1111/j.1399-0039.2004.00246.x
doi: 10.1111/j.1399-0039.2004.00246.x
pubmed: 15245369
Kaur G, Sarkar N, Bhatnagar S et al (2002) Pediatric celiac disease in India is associated with multiple DR3-DQ2 haplotypes. Hum Immunol 63(8):677–682. https://doi.org/10.1016/s0198-8859(02)00413-5
doi: 10.1016/s0198-8859(02)00413-5
pubmed: 12121676
Kanga U, Vaidyanathan B, Jaini R, Menon PSN, Mehra NK (2004) HLA haplotypes associated with type 1 diabetes mellitus in north Indian children. Hum Immunol 65(1):47–53. https://doi.org/10.1016/j.humimm.2003.10.013
doi: 10.1016/j.humimm.2003.10.013
pubmed: 14700595
Erlich HA, Valdes AM, McDevitt SL et al (2013) Next generation sequencing reveals the association of DRB3*02:02 with type 1 diabetes. Diabetes 62(7):2618–2622. https://doi.org/10.2337/db12-1387
doi: 10.2337/db12-1387
pubmed: 23462545
pmcid: 3712046
Alshiekh S, Maziarz M, Geraghty DE, Larsson HE, Agardh D (2021) High-resolution genotyping indicates that children with type 1 diabetes and celiac disease share three HLA class II loci in DRB3, DRB4 and DRB5 genes. HLA 97(1):44–51. https://doi.org/10.1111/tan.14105
doi: 10.1111/tan.14105
pubmed: 33043613
Noble JA, Valdes AM (2011) Genetics of the HLA region in the prediction of type 1 diabetes. Curr Diab Rep 11(6):533–542. https://doi.org/10.1007/s11892-011-0223-x
doi: 10.1007/s11892-011-0223-x
pubmed: 21912932
pmcid: 3233362
Guo Y, Luo R, Corsi DJ, Retnakaran R, Walker MC, Wen SW (2020) Caucasian and Asian difference in role of type 1 diabetes on large-for-gestational-age neonates. BMJ Open Diabetes Res Care. https://doi.org/10.1136/bmjdrc-2020-001746
doi: 10.1136/bmjdrc-2020-001746
pubmed: 33214189
pmcid: 7678233
Park Y, Eisenbarth GS (2001) Genetic susceptibility factors of Type 1 diabetes in Asians. Diabetes Metab Res Rev 17(1):2–11. https://doi.org/10.1002/1520-7560(2000)9999:9999%3c::aid-dmrr164%3e3.0.co;2-m
doi: 10.1002/1520-7560(2000)9999:9999<::aid-dmrr164>3.0.co;2-m
pubmed: 11241886
Steck AK, Rewers MJ (2011) Genetics of type 1 diabetes. Clin Chem 57(2):176–185. https://doi.org/10.1373/clinchem.2010.148221
doi: 10.1373/clinchem.2010.148221
pubmed: 21205883
pmcid: 4874193
Hyttinen V, Kaprio J, Kinnunen L, Koskenvuo M, Tuomilehto J (2003) Genetic liability of type 1 diabetes and the onset age among 22,650 young Finnish twin pairs: a nationwide follow-up study. Diabetes 52(4):1052–1055. https://doi.org/10.2337/diabetes.52.4.1052
doi: 10.2337/diabetes.52.4.1052
pubmed: 12663480
Girdhar K, Huang Q, Chow IT et al (2022) A gut microbial peptide and molecular mimicry in the pathogenesis of type 1 diabetes. Proc Natl Acad Sci U S A 119(31):e2120028119. https://doi.org/10.1073/pnas.2120028119
doi: 10.1073/pnas.2120028119
pubmed: 35878027
pmcid: 9351354
Yenyuwadee S, Sanchez-Trincado Lopez JL, Shah R, Rosato PC, Boussiotis VA (2022) The evolving role of tissue-resident memory T cells in infections and cancer. Sci Adv 8(33):eabo5871. https://doi.org/10.1126/sciadv.abo5871
doi: 10.1126/sciadv.abo5871
pubmed: 35977028
pmcid: 9385156
Weisberg SP, Carpenter DJ, Chait M et al (2019) Tissue-resident memory T cells mediate immune homeostasis in the human pancreas through the PD-1/PD-L1 pathway. Cell Rep 29(12):3916-3932.e5. https://doi.org/10.1016/j.celrep.2019.11.056
doi: 10.1016/j.celrep.2019.11.056
pubmed: 31851923
pmcid: 6939378
Lu J, Zhang C, Li L, Xue W, Zhang C, Zhang X (2017) Unique features of pancreatic-resident regulatory T cells in autoimmune type 1 diabetes. Front Immunol 8:1235. https://doi.org/10.3389/fimmu.2017.01235
doi: 10.3389/fimmu.2017.01235
pubmed: 29033948
pmcid: 5626883
Tandon N, Shtauvere-Brameus A, Hagopian WA, Sanjeevi CB (2002) Prevalence of ICA-12 and other autoantibodies in north Indian patients with early-onset diabetes. Ann N Y Acad Sci 958:214–217. https://doi.org/10.1111/j.1749-6632.2002.tb02972.x
doi: 10.1111/j.1749-6632.2002.tb02972.x
pubmed: 12021109
Goswami R, Kochupillai N, Gupta N, Kukreja A, Lan M, Maclaren NK (2001) Islet cell autoimmunity in youth onset diabetes mellitus in Northern India. Diabetes Res Clin Pract 53(1):47–54. https://doi.org/10.1016/s0168-8227(01)00235-2
doi: 10.1016/s0168-8227(01)00235-2
pubmed: 11378213
Maszyna F, Hoff H, Kunkel D, Radbruch A, Brunner-Weinzierl MC (2003) Diversity of clonal T cell proliferation is mediated by differential expression of CD152 (CTLA-4) on the cell surface of activated individual T lymphocytes. J Immunol 171(7):3459–3466. https://doi.org/10.4049/jimmunol.171.7.3459
doi: 10.4049/jimmunol.171.7.3459
pubmed: 14500641
Riley JL, Mao M, Kobayashi S et al (2002) Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors. Proc Natl Acad Sci U S A 99(18):11790–11795. https://doi.org/10.1073/pnas.162359999
doi: 10.1073/pnas.162359999
pubmed: 12195015
pmcid: 129347
Baharlou R, Ahmadi-Vasmehjani A, Davami MH et al (2016) Elevated levels of T-helper 17-associated cytokines in diabetes type I patients: indicators for following the course of disease. Immunol Invest 45(7):641–651. https://doi.org/10.1080/08820139.2016.1197243
doi: 10.1080/08820139.2016.1197243
pubmed: 27611173
Vorobjova T, Tagoma A, Oras A et al (2019) Celiac disease in children, particularly with accompanying type 1 diabetes, is characterized by substantial changes in the blood cytokine balance, which may reflect inflammatory processes in the small intestinal mucosa. J Immunol Res 2019:6179243. https://doi.org/10.1155/2019/6179243
doi: 10.1155/2019/6179243
pubmed: 31214623
pmcid: 6535873
Wang L, Wang HL, Liu TT, Lan HY (2021) TGF-beta as a master regulator of diabetic nephropathy. Int J Mol Sci. https://doi.org/10.3390/ijms22157881
doi: 10.3390/ijms22157881
pubmed: 35008882
pmcid: 8745061
Bonfiglio V, Platania CBM, Lazzara F et al (2020) TGF-β serum levels in diabetic retinopathy patients and the role of anti-VEGF therapy. Int J Mol Sci. https://doi.org/10.3390/ijms21249558
doi: 10.3390/ijms21249558
pubmed: 33374380
pmcid: 7795544
Zorena K, Malinowska E, Raczyńska D, Myśliwiec M, Raczyńska K (2013) Serum concentrations of transforming growth factor-Beta 1 in predicting the occurrence of diabetic retinopathy in juvenile patients with type 1 diabetes mellitus. J Diabetes Res 2013:614908. https://doi.org/10.1155/2013/614908
doi: 10.1155/2013/614908
pubmed: 23671881
pmcid: 3647575